Platelet-derived microparticles (PDMPs) are released from platelets in association with platelet activation, the contents of which include platelet granular proteins such as P-selectin, and various platelet surface membrane glycoproteins such as glycoprotein (GP)Ib/IX or GPIIb/IIIa1. PDMPs are not merely a marker for platelet activation but also have pro-coagulant activity, and thereby, contribute to thrombus formation2. In addition, PDMPs participate in the inflammatory process as a mediator of platelet-leukocyte, leukocyte-endothelial cell or leukocyte-leukocyte interactions1. PDMPs stimulate cytokine production and enhance the expression of cell adhesion molecules including leukocyte integrin Mac-I (CD 11 b/CD18, αMβ2)3. Although PDMPs are usually determined by flow cytometry, circulating PDMPs are also measured by enzyme-linked immunosorbent assay (ELISA) using two antibodies against the platelet membrane surface glycoproteins, GPIb and GBIX4. Despite increased research activity on the characteristics of PDMPs, the clinical significance of the measurement of circulating PDMPs has not yet been established.
Percutaneous coronary intervention (PCI) produces significant inflammatory reaction in the injured vessel wall, which triggers acute ischemic events and late restenosis5, 6. In the process of inflammation at the site of PCI-induced injury, the activation of leukocytes, neutrophils as well as monocytes, and their interaction with platelets mediated by cell adhesion molecules are known to play an important causative role in the development of restenosis. There is increasing evidence that the interaction between platelets and leukocytes across an adherent layer of platelets precedes diapedesis and the infiltration of inflammatory cells into the PCI-injured vessel wall, which is denuded of vascular endothelial cells by balloon inflation or stenting7, 9. Among various adhesion molecules, leukocyte Mac-1 is of particular importance in the process of transplatelet migration. Mac-1 orchestrates the recruitment of leukocytes by binding to platelet ligands, such as GPIbα 10, to promote firm adhesion at sites of vessel wall injury. Monoclonal antibody blockade 11 and the absence of Mac-1 12 reduce neointimal thickening after experimental angioplasty and stenting. The inventors demonstrated previously that PCI-induced activation and up-regulation of Mac-1 on the surface of neutrophils reached a maximum 48 hrs after PCI and was associated with restenosis 13-18
Since GPIbα, a platelet ligand for leukocyte Mac-1, is expressed on the surface of PDMPs, the inventors hypothesized that circulating PDMPs could be linked to Mac-1 expressed on the surface of leukocytes, and could play an important role in the process of inflammation associated with arteriosclerosis.